The complications of diabetes mellitus are characterized by alterations in cell proliferation and function. Decreased levels of the insulin-like growth factors (NSILA-S, somato-medin A and somatomedin C) may be responsible for some of these complications. These peptides, under partial growth hormone control may also require insulin for their synthesis. The levels of these peptides in human serum have been difficult to measure because of limitations of the bioassays, radioreceptor assays and radioimmunoassays, as well as the inaccesibility of the latter. To study the role of the insulin-like growth factors in diabetes I plan to measure the levels of these peptides in human serum and to treat diabetic animals with purified factors. I have devised a new method for the purification of these proteins, using the natural affinity of these hormones for their binding protein. A radioimmunoassay for one of them has been developed and I have begun to apply this to clinical conditions. I plan to develop an RIA for another, and to measure the serum levels in diabetic patients, in a variety of natural and provocative situations. Conditions to be studied will include the growth retardation characteristic of poor control of juvenile diabetes and diabetic complications such as diabetic retinopathy. The large amounts of peptides generated, will allow us to use these as replacement hormones in animal models that simulate diabetic growth retardation. The effect of IGF on somatic and bone growth will be studied.